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Blood-derived plasminogen drives brain inflammation and plaque deposition in a mouse model of Alzheimer's disease
Baker SK, Chen ZL, Norris EH, Revenko AS, MacLeod AR, Strickland S.. Proceedings of the National Academy of Sciences of the United States of America, 2018-09-25
Topic: Brain proteins, microglia and lab models
Two of the most predominant features of the Alzheimer's disease (AD) brain are deposition of β-amyloid (Aβ) plaques and inflammation. The mechanism behind these pathologies remains unknown, but there is evidence to suggest that inflammation may predate the deposition of Aβ. Furthermore, immune activation is increasingly being recognized as a major contributor to the pathogenesis of the disease, and disorders involving systemic inflammation, such as infection, aging, obesity, atherosclerosis, diabetes, and depression are risk factors for the development of AD. Plasminogen (PLG) is primarily a blood protein synthesized in the liver, which when cleaved into its active form, plasmin (PL), plays roles in fibrinolysis, wound healing, cell signaling, and inflammatory regulation. Here we show that PL in the blood is a regulator of brain inflammatory action and AD pathology. Depletion of PLG in the plasma of an AD mouse model through antisense oligonucleotide technology dramatically improved AD pathology and decreased glial cell activation in the brain, whereas an increase in PL activity through α-2-antiplasmin (A2AP) antisense oligonucleotide treatment exacerbated the brain's immune response and plaque deposition. These studies suggest a crucial role for peripheral PL in mediating neuroimmune cell activation and AD progression and could provide a link to systemic inflammatory risk factors that are known to be associated with AD development.
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APA 7th
Baker, S. K., Chen, Z. L., Norris, E. H., Revenko, A. S., MacLeod, A. R., & Strickland, S. (2018). Blood-derived plasminogen drives brain inflammation and plaque deposition in a mouse model of Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1811172115
Vancouver
Baker SK, Chen ZL, Norris EH, Revenko AS, MacLeod AR, Strickland S. Blood-derived plasminogen drives brain inflammation and plaque deposition in a mouse model of Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America. 2018. doi:10.1073/pnas.1811172115. PMID: 30254165.
BibTeX
@article{baker2018-30254165,
author = {Baker, S. K. and Chen, Z. L. and Norris, E. H. and Revenko, A. S. and MacLeod, A. R. and Strickland, S.},
title = {{Blood-derived plasminogen drives brain inflammation and plaque deposition in a mouse model of Alzheimer's disease}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2018},
doi = {10.1073/pnas.1811172115},
pmid = {30254165},
url = {https://doi.org/10.1073/pnas.1811172115}
}
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Key findings
- The mechanism behind these pathologies remains unknown, but there is evidence to suggest that inflammation may predate the deposition of Aβ.
- These studies suggest a crucial role for peripheral PL in mediating neuroimmune cell activation and AD progression and could provide a link to systemic inflammatory risk factors that are known to be associated with AD development.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30254165) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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